TY - JOUR
T1 - Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile
T2 - A longitudinal MRI study
AU - Tosun, Duygu
AU - Schuff, Norbert
AU - Truran-Sacrey, Diana
AU - Shaw, Leslie M.
AU - Trojanowski, John Q.
AU - Aisen, Paul
AU - Peterson, Ronald
AU - Weiner, Michael W.
N1 - Funding Information:
Dr. Schuff received honoraria from the Michael J. Fox foundation, the British Research Council, and Elsevier Publishing company; receives research support from The Michael J. Fox foundation , and Department of Defense (WX), P41 RR023953 (Coinvestigator); P50AG23501 (Coninvestigator).
Funding Information:
This work is funded by the National Institutes of Health (NIH), National Institute of Biomedical Imaging and Bioengineering (NIBIB) [ T32 EB001631-05 ].
Funding Information:
Dr. Weiner serves on scientific advisory boards for Bayer Schering Pharma, Eli Lilly, Nestle, CoMentis, Neurochem, Eisai, Avid, Aegis, Genentech, Allergan, Lippincott, Bristol Meyers Squibb, Forest, Pfizer, McKinsey, Mitsubishi, and Novartis. He has received nonindustry-supported funding for travel; serves on the editorial board of Alzheimer's & Dementia; received honoraria from the Rotman Research Institute and BOLT International; receives research support from Merck & Co, Avid , NIH [ U01AG024904 (PI), P41 RR023953 (PI), R01 AG10897 (PI), P01AG19724 (Coinvestigator), P50AG23501 (Coinvestigator), R24 RR021992 (Coinvestigator), R01 NS031966 (Coinvestigator), and P01AG012435 (Coinvestigator)], the Department of Defense [ DAMD17-01-1-0764 (PI)], and the Veterans Administration [MIRECC VISN 21 (Core PI)]; and holds stock in Synarc and Elan Pharmaceuticals.
Funding Information:
Data collection and sharing for this project was funded by the Alzheimer's disease Neuroimaging Initiative (ADNI) ( National Institutes of Health , Grant U01 AG024904 ). ADNI is funded by the National Institute on Aging , the National Institute of Biomedical Imaging and Bioengineering , and through generous contributions from the following: Abbott , AstraZeneca AB , Bayer Schering Pharma AG , Bristol-Myers Squibb , Eisai Global Clinical Development , Elan Corporation , Genentech , GE Healthcare , GlaxoSmithKline , Innogenetics , Johnson and Johnson , Eli Lilly, and Co. , Medpace, Inc. , Merck and Co., Inc. , Novartis AG , Pfizer Inc , F. Hoffman-La Roche , Schering-Plough , Synarc, Inc. , and Wyeth , as well as nonprofit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation , with participation from the US Food and Drug Administration . Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org/ ). The grantee organization is the Northern California Institute for Research and Education , and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 , K01 AG030514 , and the Dana Foundation .
PY - 2010/8
Y1 - 2010/8
N2 - Previously it was reported that Alzheimer's disease (AD) patients have reduced beta amyloid (Aβ1-42) and elevated total tau (t-tau) and phosphorylated tau (p-tau181p) in the cerebrospinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly individuals and those with mild cognitive impairment (MCI). In this study, we tested the hypothesis that there would be an association among rates of regional brain atrophy, the CSF biomarkers Aβ1-42, t-tau, and p-tau181p and apolipoprotein E (ApoE) ε4 status, and that the pattern of this association would be diagnosis-specific. Our findings primarily showed that lower CSF Aβ1-42 and higher tau concentrations were associated with increased rates of regional brain tissue loss and the patterns varied across the clinical groups. Taken together, these findings demonstrate that CSF biomarker concentrations are associated with the characteristic patterns of structural brain changes in healthy elderly and mild cognitive impairment subjects that resemble to a large extent the pathology seen in AD. Therefore, the finding of faster progression of brain atrophy in the presence of lower Aβ1-42 levels and higher tau levels supports the hypothesis that CSF Aβ1-42 and tau are measures of early AD pathology. Moreover, the relationship among CSF biomarkers, ApoE ε4 status, and brain atrophy rates are regionally varying, supporting the view that the genetic predisposition of the brain to beta amyloid and tau mediated pathology is regional and disease stage specific.
AB - Previously it was reported that Alzheimer's disease (AD) patients have reduced beta amyloid (Aβ1-42) and elevated total tau (t-tau) and phosphorylated tau (p-tau181p) in the cerebrospinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly individuals and those with mild cognitive impairment (MCI). In this study, we tested the hypothesis that there would be an association among rates of regional brain atrophy, the CSF biomarkers Aβ1-42, t-tau, and p-tau181p and apolipoprotein E (ApoE) ε4 status, and that the pattern of this association would be diagnosis-specific. Our findings primarily showed that lower CSF Aβ1-42 and higher tau concentrations were associated with increased rates of regional brain tissue loss and the patterns varied across the clinical groups. Taken together, these findings demonstrate that CSF biomarker concentrations are associated with the characteristic patterns of structural brain changes in healthy elderly and mild cognitive impairment subjects that resemble to a large extent the pathology seen in AD. Therefore, the finding of faster progression of brain atrophy in the presence of lower Aβ1-42 levels and higher tau levels supports the hypothesis that CSF Aβ1-42 and tau are measures of early AD pathology. Moreover, the relationship among CSF biomarkers, ApoE ε4 status, and brain atrophy rates are regionally varying, supporting the view that the genetic predisposition of the brain to beta amyloid and tau mediated pathology is regional and disease stage specific.
KW - Alzheimer's disease
KW - ApoE
KW - Atrophy
KW - Biomarkers
KW - Brain tissue volume
KW - Cerebrospinal fluid
KW - Cortical thickness
KW - Healthy aging
KW - MRI
KW - Mild cognitive impairment
UR - http://www.scopus.com/inward/record.url?scp=77954030909&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954030909&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2010.04.030
DO - 10.1016/j.neurobiolaging.2010.04.030
M3 - Article
C2 - 20570401
AN - SCOPUS:77954030909
VL - 31
SP - 1340
EP - 1354
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 8
ER -